1. Technical Field
The present invention relates to a peptide useful for promoting osteoporosis or vascularization and the use thereof.
2. Description of the Related Art
Bones constitute part of the endoskeleton which physically supports the body, and play an important role in maintaining the blood calcium level. In a normal state, bones exhibit dynamic homeostasis in which both bone resorption and formation actively proceed in metabolic balance. The disruption of the balance between bone resorption and formation with a shift towards bone resorption causes a decrease in bone mineral density or bone mass and bone strength, leading to osteoporosis.
Osteoporosis is a bone disease characterized by the high risk of fracture upon receiving just a slight impact as a result of weakened bones. Other representative bone diseases are osteoarthritis and bone defects. Osteoarthritis, also known as degenerative arthritis, is characterized by a local degenerative change in the joint as a result of the breakdown and loss of cartilage. Bone defects may form in many sites of the body, predominantly because of acute trauma with the accompaniment of bone matrix loss, acute trauma with the accompaniment of surgical bone loss, chronic infection with the accompaniment of bone resection, and chronic nonunion with the accompaniment of segmental defects.
The market associated with bone disease around the world amounts to approximately 130 billion dollars and it is expected to continuously expand in size. Thus, research institutes and pharmaceutical companies have made tremendous investments in the development of medicines for bone diseases.
Medicines currently used for osteoporosis include bisphosphonates (alendroate, etidronate, etc.), hormonal agents (raloxifene), vitamin D agents, calcitonin agents and calcium agents. Recently, the parathyroid hormone agent FORTEO™ has been commercially available and has an ability to form new bones.
However, bisphosphonates have a problem associated with the uptake thereof in that because bisphosphonates are absorbed at a very low rate and cause erosion of the esophagus, the patients must take them together with a sufficient amount of water and sit upright for a time after the uptake of the medication. Hormonal agents are required to be taken over the entire lifespan of the patients and the administration thereof over the long term may cause side effects such as breast cancer, uterine cancer, and thrombosis. Vitamin D agents are very expensive, and their pharmaceutical efficacy is not reliable. Calcitonin agents are also expensive and have a problem associated with the administration thereof. Calcium agents do not engender significant side effects, but are limited to prophylactic effects rather than therapeutic effects.
The parathyroid hormone agent, FORTEO™, which has recently been commercialized, can induce bone formation and thus has an advantage over conventional drugs that work to prevent bone resorption. However, it suffers from the disadvantages of being administered by daily injection over a long period of time and being very expensive. There is therefore the need for a novel medication and method that can increase bone mass and improve bone quality to substantially reduce the risk of fracture, thus being applicable to the treatment of osteoporosis.
Ischemic diseases are caused by locally restricting the blood supply as a result of various pathological abnormalities in the blood vessels, with resultant damage or malfunction of tissues. Blood supply through vessels is essential for wound healing or tissue regeneration. Vascular diseases, such as arteriosclerosis, myocardial infarction, and angina pectoris are caused by restricted blood flow.
Vascular therapy is used to treat diseases by generating vessels. Vascular endothelial growth factor (VEGF) is already used as a therapeutic for severe ischemia. Other vasculogenic or angiogenic factors such as fibroblast growth factor (FGF), epidermal growth factor (EGF) and platelet-derived endothelial growth factor (PDEGF) have also been studied for purposes of clinical use. However, these factors are proteins and so are difficult to separate and purify. In addition, they are too expensive for clinical application.
Leading to the present invention, intensive and thorough research into the treatment of bone diseases and ischemic diseases, conducted by the present inventors under the background, resulted in the finding that BFP 4 (bone forming peptide 4) can be economically synthesized and has the activity of promoting osteogenesis and vascularization.